1. Field of the Disclosure
The disclosure generally relates to an improvement in dialysis and, more specifically, to an apparatus and method of increasing dialysis dose and solute clearance with the introduction of mechanical energy, such as vibration, to a hemodiafiltration membrane.
2. Brief Description of Related Technology
The human kidneys remove waste products of bodily metabolism and regulate the concentrations of most of the constituents of the body's fluids. Dialysis is the process of removing these waste products with special equipment. The two major forms of dialysis are hemodialysis and peritoneal dialysis. Hemodialysis is a medical procedure that uses a machine (e.g., a dialyzer) to filter waste products from the bloodstream and restore the blood's normal components. Hemodialysis is often a necessary and inconvenient form of treatment for those patients suffering end-stage renal disease (ESRD) or other kidney disorders.
A conventional hemodialysis apparatus includes a blood circuit to extracorporeally circulate a patient's blood, a dialyzer provided at the blood circuit, a blood pump, and a dialysis device. The dialysis device allows a dialysate (dialysis solution) to flow into and out of the dialyzer from the dialysis device to perform hemodialysis and, optionally, ultrafiltration, together collectively known as hemodiafiltration. The blood circuit includes blood accessed from a venous access site a by a needle and pumped through tubing into the blood side of the hemodialyzer. Blood that has been dialyzed is returned to the patient via blood tubing that is connected to a needle into another venous access site.
Generally, hemodialysis includes directing blood drawn from the body of a patient through an extracorporeal blood circuit and through a dialyzer (for filtering) before being returned to the venous system of the patient. More specifically, when the needles are inserted into the patient, and the blood pump is turned on, pre-dialyzed blood of the patient flows through a first needle into the pre-dialyzed blood circuit, the dialyzer, and the venous blood circuit in sequence, and then flows back into the body of the patient through another venous needle. Hollow-fiber dialyzers and plate dialyzers are two types of dialyzers that may be utilized in an extracorporeal blood circuit during hemodialysis, although hollow-fiber dialyzers are more common today. A hollow-fiber dialyzer typically includes bundles of capillary tubes through which blood travels, while a plate dialyzer generally includes membrane sheets arranged in a parallel-plate configuration.
Within a hollow-fiber dialyzer, the blood flows through a plurality of hollow fibers contained within a plastic module (or housing, shell, or jacket). The dialysate is supplied from the dialysis device, flows outside the hollow fibers (i.e., between outside surfaces of the hollow fibers and an inside surface of the plastic module of the dialysis device). Waste products in the blood flowing inside the hollow fibers permeate (via convection and/or diffusion) into the dialysate through the membranes. The blood flows back to the patient's body after flowing through the venous blood circuit and after the waste products have been removed from the blood. Each hollow fiber, or membrane, typically includes a semi-permeable tube having a non-uniform thickness as well as non-uniform pore sizes and pore distribution. Cellulosic membranes and synthetic polymer membranes are examples of membranes commercially available and commonly used in hemodialysis.
The dialysate may, for example, include a mixture of electrolytes such as, for example, bicarbonate, sodium, potassium, calcium, magnesium, chloride, and dextrose. As blood flows through the hollow fibers, toxins, especially low molecular weight toxins, are removed from the blood primarily via diffusive transport and secondarily via convective transport. For example, during hemodialysis, uremic solutes transfer from the blood side to the dialysate side of the hemodiafiltration membrane. Uremic solutes responsible for uremic toxicity are usually classified Into groups based on their molecular weights (MW). Low molecular weight solutes have molecular weights less than 500 Daltons (Da). Examples include urea (60 Da) and creatinine (113 Da). Middle molecular weight solutes have molecular weights ranging from 500 to 15,000 Da. An example includes β2-microglobulin.
Molecules normally cleared by the kidneys are retained in the body during renal failure and can lead to morbidity and mortality. Because dialysis primarily uses diffusion to clear waste products and other solutes, the dialytic clearance of these molecules is dependent on their molecular weight. Middle molecular weight solutes are more difficult to clear by dialysis than low molecular weight solutes, like urea. These middle molecular weight solutes may be an important contributor to the uremic syndrome. Vanholder et al. (1995) Artif. Organs 19:1120-25.
Assessing the clearance of those molecules is a key issue in the management of dialysis patients, as urea removal is measured routinely to quantify the “dose” of dialysis that a patient receives. Dialysis dose must be individualized for each patient. Dialysis dose is commonly expressed as Kt/Vurea, where K represents the rate of urea clearance by the dialyzer (in mL/min), t is the duration of dialysis (in minutes), and Vurea is the volume of distribution of urea (mL). Gotch (2000) Blood Purif. 18:276-85. Consequently, Kt/Vurea is a unitless value, but one that has shown to have good correlation with outcome of patients with ESRD. See Hakim et al. (1994) Am J Kidney Dis 5:661-69; Parker, III, et al. (1994) Am J Kidney Dis 5:670-80. A dialysis dose (Kt/Vurea) of about 1.2 for each hemodialysis treatment (three times weekly) is the standard for dialysis adequacy according to the Kidney Disease Outcomes Quality Initiative group (National Kidney Foundation). See National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy Am J Kidney Dis (2001) 37(Suppl. 1):S7-S64.
The dialysis dose can be influenced only by modifying clearance (K) or duration of dialysis (t). The volume of distribution (V) of urea in the body is specific to the patient as it is approximately equal to the volume of total body water (in mL). Thus, volume distribution (V) cannot be manipulated to increase the dialysis dose.
Duration of dialysis (t) can be lengthened to increase dialysis dose. For example, if the Kt/Vurea, is 0.9, and one wished to attain a Kt/Vurea of 1.2, then the duration of dialysis (t) would need to be increased by 33%, assuming that clearance (K) remains the same. Although this would be an easy way to increase the dose, in many cases it is not practical. Patients with ESRD would have to be willing to either receive dialysis for a longer duration per session or receive it more often (e.g., than three times a week). Not only would this inconvenience the patient, but it would also put a strain on dialysis units, which often already run three 4-hour dialysis shifts/day. Patients with acute renal failure (ARF) often receive continuous renal replacement therapy (CRRT) for 24-hours per day and, thus, the duration of dialysis can be extended no further for these patients.
Manipulating the dialyzer clearance (K) is the only practical way to increase the dialysis dose. In conventional hemodialysis, blood flow rate has a profound effect on dialyzer clearance (K). Blood flow rate is often limited in ESRD patients because of vascular access considerations. Once sufficient blood flow is achieved, further modest increases in dialyzer clearance (K) can be obtained by increasing dialysate flow rate or by using dialyzers with larger hemodiafiltration membrane surface areas. Many solute-related variables can influence the dialytic clearance. Among the more important of these variables are the molecular weight of the molecules being cleared, ionization state, extent of protein binding, and concentration gradient. Solute-related variables, however, cannot be manipulated to change dialysis dose. Other variables, such as blood flow rate, dialysate flow rate, and dialyzer characteristics such as pore size (permeability), tortuosity of dialyzer fibers, and surface area, determine urea clearance (K). Daugirdas et al., Handbook of Dialysis, 3d Ed. (Lippincott Williams and Wilkins, 2001). Many of these variables are presently manipulated to increase the interaction of the solutes with the membrane to increase diffusion across the dialyzer, resulting in greater clearance of solutes and, thus, a greater dialysis dose. And while these manipulations can aid in improvements in dialysis, each, of course, has its limits. Consequently, improvements achievable independent of these variables and the other variables discussed above would certainly be desirable.